The primary goal of the proposed research is to further understand the neurobiological basis of cognitive aging. Neural substrates underlying age-related working memory (WM) differences will be examined using the framework of the neural efficiency hypotheses, which states that reduced efficiency of cortical functioning underlies slower speed of processing in older versus younger adults, which in turn mediates age- related cognitive declines. The proposed research will advance this hypothesis using diffusion tensor imaging (DTI) in combination with functional magnetic resonance imaging (fMRI) to assess the contribution of white matter integrity to neural efficiency. Age-related slowing has been proposed to account for cognitive aging, including age-related WM declines. However, the neural basis of this effect has not been systematically examined. FMRI research has shown that prefrontal (PFC) and parietal cortex mediate WM performance, and that activity in these regions is modulated by WM performance speed and processing speed. We propose that the relationship between processing speed and the magnitude of neural activity may reflect efficiency of neural functioning, which may underlie age group differences in WM. The proposed experiment will be the first to directly test whether individual differences in neural efficiency, measured as processing speed-related PFC activity, mediates WM declines in aging (Specific Aim 1). The neural efficiency hypothesis further proposes that age-related neural efficiency declines may be due to age group differences in underlying brain structure, such as integrity of white matter connections between task-relevant brain regions. DTI research has shown that integrity of frontal white matter declines with aging, and is associated with impaired processing speed and WM in older versus younger adults. The proposed study will be the first to examine whether age group differences in integrity of task-relevant frontal-parietal tracts relates to neural efficiency, and whether this explains age group differences in WM performance (Specific Aim 2). These long-range direct connections may be more susceptible to age-related declines in integrity, which may lead to increased dependence on indirect connections (i.e., frontal-thalamus-parietal) for optimal task performance. Therefore, this study will also assess relationships among indirect tract integrity, neural efficiency, and WM performance in aging (Specific Aim 3). Results from this study will contribute to fostering successful aging. WM is integral to a variety of everyday skills including reasoning, language comprehension, and mental calculations. Identifying functional and structural neural mechanisms underlying optimal performance will inform cognitive training and pharmacological treatment programs aimed at maximizing cognitive functioning in old age. This goal is becoming increasingly important as the number of older adults in our population steadily rises. PUBLIC HEALTH RELEVANCE: Results from this study are relevant to successful aging. Working memory promotes independent living by enabling people to perform a variety of everyday skills including reasoning, language comprehension, and mental calculations. Thus, identifying the neural mechanisms underlying optimal performance is important for cognitive training and pharmacological treatment programs aimed at maximizing cognitive functioning in old age. This goal is becoming increasingly important as the number of older adults in our population steadily rises.